[Plasma catecholamines in kidney insufficiency].
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Biomedical subjects
Publications and source records attributed to D Ratge.
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14 normal volunteers, 23 patients with euthyroid goiter, 9 patients with hypothyroidism and 17 patients with hyperthyroidism were injected with 400 micrograms thyroliberin (thyrotropin releasing hormone, TRH). The documented side effects were the same in all the 4 groups studied. Subjective symptoms such as flushing, nausea, urinary urgency, dizziness and headache in decreasing sequence were mentioned by 86% of subjects. Shortly after thyroliberin injection, a mean increase of 26 +/- 13 mm Hg for systolic and 14 +/- 6 mm Hg for diastolic blood pressure as well as an increased heart rate by 7.2 +/- 6.6 min-1 was demonstrated. Plasma catecholamines were lowered in patients with euthyroid goiter and hyperthyroidism and raised in patients with hypothyroidism, compared with the controls. Thyroliberin administration was associated with an activation of the sympathoadrenal system. The increments in plasma epinephrine and norepinephrine concentrations were proportional to initial values, but were insufficient to affect blood pressure. The mean increase of 28% for plasma epinephrine and 21% for norepinephrine were maximal in the second to the forth minute, where subjective symptoms, blood pressure and heart rate were already decreasing. In view of the rapid onset of the subjective symptoms as well as the chronotropic and the pressor response, thyroliberin may partly exert these effects centrally or directly on the vascular system, independently of catecholamines. Since individual systolic blood pressure increased by as much as 64 mm Hg, caution is advised in selecting patients with risk factors for testing.
Autonomic system dysfunction could be the cause of postural hypotension seen in patients on continuous ambulatory peritoneal dialysis (CAPD). To verify this hypothesis, we examined the alpha 2- and beta 2-adrenoceptors on blood cells after 1/2 h in the resting supine position with the peritoneal cavity filled for 2-3 h, as well as the response of plasma norepinephrine (NE), heart rate (HR) and mean arterial blood pressure (MAP) to 10 min of standing. Supine free and particularly conjugated NE levels were significantly higher in all uremic patients compared with controls. The postural test induced similar increases of MAP and HR in 8 diabetic, 11 nondiabetic patients and 23 controls, whereas 4 diabetic patients became hypotensive. Orthostasis caused a mean free NE increment of only 0.5 nmol/l in the latter patient group with mean NE responses of 1.45-1.65 nmol/l in the former 3 groups. The densities of platelet alpha 2-adrenoceptors (assessed by [3H] yohimbine binding) and of mononuclear leucocyte (MNL) beta 2-adrenoceptors determined by (-) (125I) iodocyanopindolol binding amounted to 160 +/- 50 and 1600 +/- 520 binding sites/cell, respectively, in controls and were unchanged in patients without postural hypotension. The 4 diabetic patients suffering from postural hypotension showed numerically higher beta 2-receptor numbers (2080 binding sites/cell), significantly increased alpha 2-receptor densities (280 binding sites/cell, p less than 0.05) and significantly increased MNL isoproterenol-stimulated adenylate cyclase activities (38 vs 24 pmol cAMP/10(6) MNL/10 min in controls, p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
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Plasma free and sulfoconjugated norepinephrine (NE), epinephrine (E) and dopamine (DA) concentrations measured in patients with thrombocytopenia or thrombocytosis, in newborns and pregnant women were not statistically different from values determined in 41 healthy volunteers. The percentage free to total NE, E and DA was 30 +/- 10%, 35 +/- 11% and 1.5 +/- 1.1% (mean +/- SE) in the controls, resp; not different from the previously described patients or from patients with liver failure who showed significantly higher free and conjugated NE and E levels when compared with controls (p less than 0.01, resp.). Conjugated catecholamine (CA) levels from the femoral artery and from multiple sites in the venous system sampled in patients undergoing intracardiac measurements were identical. The data suggest that sulfation of CA may not be simply ascribed to platelets, to the liver, to vascular beds, or to organs along the vena cava including the adrenal glands. The parallel increase of free and conjugated NE with age in healthy controls, as well as the unchanged degree of conjugation in patients with increased spillover of NE and E caused by a pheochromocytoma or by a heart attack, suggest that there is a balance between free and sulfated CA. A normal ratio of free to conjugated NE and E observed in patients receiving high dosage DA infusion further indicates that there is an adequate sulfate supply and no apparent substrate inhibition of the conjugation process. Because the percentage free of total NE, E and DA were significantly lower in patients in the hypothyroid state when compared with controls (p less than 0.01, resp.), hypothyroidism may affect the balance of free to conjugated CA in a yet unknown way.
To investigate changes of free and sulfoconjugated catecholamines in response to alterations in sympatho-adrenal activity, free and conjugated noradrenaline, adrenaline and dopamine were determined radioenzymatically in plasma of 49 subjects. During brief vigorous bicycle exercise (8 min, maximal heart rate: 177 beats/min) mean free noradrenaline and adrenaline values of 2.0 and 0.51 nmol/l at rest, increased to 6.7 and 2 nmol/l (P less than 0.001) respectively, at the maximal workload of 200 watt, whereas conjugated noradrenaline and adrenaline decreased from 3.4 and 0.8 nmol/l to 2.1 and 0.4 nmol/l (P less than 0.001) respectively. In the tenth min of the recovery period basal free and conjugated noradrenaline and adrenaline levels were measured. The moderate stress of a steam bath (20 min, maximal heart rate: 131 beats/min) doubled free noradrenaline and adrenaline levels. However, conjugated noradrenaline and adrenaline concentrations remained unchanged. The increase in free catecholamine values during an exhausting cross-country march over 20 km was associated with an accumulation of sulfated catecholamines. After a rest of 30 min free noradrenaline and adrenaline reached basal values, whereas conjugated noradrenaline and adrenaline remained elevated by 64 and 70% respectively, compared to pre-exercise concentrations. It was concluded that conjugated noradrenaline and adrenaline may be used as pools for free noradrenaline and adrenaline during brief vigorous exercise. In addition, they may also be indicators of chronic activation of the sympatho-adrenal system.
The determination of norepinephrine and epinephrine in plasma by HPLC with amperometric detection was modified, giving detection limits of 25 ng/l for norepinephrine and epinephrine, respectively, using 1 ml plasma. In order to achieve this sensitivity, it was necessary to minimize the background noise by modification of instrumentation and specimen handling. Particularly important was the extra purification of the reagents, the application of micro-bore HPLC, the enzymatic cleavage of uric acid and temperature control of the amperometric cell and the amplifier. Comparison of the present method with the radioenzymatic determination of catecholamines resulted in coefficients of correlation of r = 0.924 and 0.919 for norepinephrine and epinephrine, resp. (n = 38). The concentrations of the 38 different samples used for the comparison were in the physiological range.
In many tissues adrenergic responsiveness may be impaired by chronic exposure to adrenergic agonists. We examined the effects of high levels of circulating norepinephrine and epinephrine to alpha 2- and beta 2-adrenoceptors on platelets and mononuclear leucocytes (MNL) of patients with phaeochromocytoma. When compared with controls the density of beta 2-receptors prior to removal of the tumour was diminished by 67% (500 +/- 160 sites/cell, n = 7 vs 1500 +/- 350 sites/cell, n = 29; P less than 0.001). Binding affinities for [3H]dihydroalprenolol (apparent KD = 0.45 +/- 0.16 nmol/l in phaeochromocytoma, 0.52 +/- 0.19 nmol/l in controls) were not significantly different in MNL preparations from the two groups. MNL adenylate cyclase activities in response to 10 mumol/l (-) isoproterenol was lower in the patients (7.5 vs 22 pmol cAMP/10(6) MNL/10 min; P less than 0.001). Conversely, the number of alpha 2-adrenoceptors on platelets and the affinity of these receptors for [3H]yohimbine did not differ between patients and controls. Ensuing adrenalectomy the regeneration of the beta-adrenergic cAMP-system results from a two-phase process. A prompt but moderate restoration was followed by a gradual rise to the normal range within about 1 to 2 months indicating the dynamic character of the beta 2-adrenoceptor cAMP-system in MNL. We conclude that the downregulation observed in MNL, which appears not to be operative in human platelets, represents only one mechanism of feedback control in the sympatho-adrenal-system protecting tissues from prolonged stimulation by excessive catecholamines.
The determination of glucose, uric acid, urea, triglycerides, cholesterol, sodium, and potassium was investigated using an Ektachem DT 60 and the Ektachem DTE-module. The coefficients of variation ranged from 0.5 to 5.3% for within run and from 1.1 to 4.7% for within day precision. The deviations of the measured values from the assigned values (determined by gas chromatography and mass spectrometry, or by interlaboratory surveys were less than 5%. The determination of urea in control samples was influenced by matrix effects, but not the analysis of patients samples. The comparative analysis of patient samples with routine methods and multilayer reagent carriers showed good agreement. The linear coefficients of correlation ranged from 0.9318 (sodium) to 0.9945 (triglycerides). The analyser is easy to use and has been proved to be very reliable. The throughput of 65 substrate and 15 electrolyte determinations per hour is sufficient for the medical practitioner or small laboratories.
In a placebo controlled, single blind, randomized cross over study catecholamines (CA) and renin activity (PRA) in plasma were measured in 2 female and 4 male healthy volunteers, at rest in the supine position, following a single intravenous injection of 0.15 mg/kg ketanserin (K) and placebo (P, 10 ml saline). K caused a significant increase in the area under the plasma norepinephrine (NE) time curve (AUCNE) from 13,200 to 18,100 ng X 1(-1) X min for 1 hour after the injection. The area under the plasma epinephrine (E) time curve (AUCE) was also increased but to a lesser extent; it was significantly elevated from 54 to 68 ng X 1(-1) X min for 1 minute after the injection. Dopamine (DA) and PRA did not show any significant response to ketanserin. Following the P injection, none of the four parameters showed any significant change.
The concentration of free and conjugated norepinephrine (NE), epinephrine (E) and dopamine (DA) were measured by a modified radio-enzymatic assay in the plasma and in the cerebrospinal fluid (CSF) of 45 patients with normal and in 21 patients with disturbed blood-CSF barriers. In patients with an undisturbed blood-CSF barrier the free NE and E in CSF were 128 +/- 45 ng/l and 27 +/- 20 ng/l (mean values +/- S.E.), respectively, and represented about 50% of the average plasma values. Mean DA was not different in plasma (47 +/- 22 ng/l) and in CSF (41 +/- 19 ng/l). Both in plasma and in CSF, considerable higher free catecholamine (CA) levels were measured in patients with dysfunction of the blood-CSF barrier. In one patient with bacterial meningitis twofold higher concentrations of free NE and DA in CSF as compared with plasma were detectable. Sulfate conjugates of catecholamines are predominant in plasma and CSF. The contribution of conjugated CA to total CA in plasma from patients with normal blood-CSF barrier averaged 69.7%, 63.1% and 98.1% for NE, E and DA, respectively and was significantly lower in the CSF (p less than 0.001). In patients with disturbed blood-CSF barrier, the increases of conjugated CA were more pronounced in CSF than in plasma. Further, the contribution of conjugated NE and E to total NE and E in CSF was not only increased in patients with bacterial meningitis, but also in patients with renal insufficiency compared to the "control" patients (p less than 0.02 and p less than 0.001 resp.). Free and conjugated NE, E and DA in the plasma and CSF were related significantly (p less than 0.01 resp.) with stronger correlation for conjugated CA (p less than 0.001 resp.). These results together with findings in the literature, suggest that there is little or no rostral-caudal gradient in CSF CA conjugate concentrations and that even in patients with intact blood-CSF barrier plasma conjugated CA concentrations influence those in CSF. Thus only free CA levels in CSF may reflect the central adrenergic activity.
The contribution of arginine vasopressin (AVP) to the maintenance of mean arterial pressure (MAP) during fluid deprivation was reinvestigated in chronically prepared, conscious, freely moving rats. In normal Long-Evans (LE) rats during water deprivation for up to 48 h plasma AVP levels increased from 2.98 +/- 0.62 to 17.55 +/- 2.03 pg/ml, but MAP and heart rate (HR) remained unchanged. Fluid deprivation for 10 h in Brattleboro homozygous rats that are unable to synthetize vasopressin resulted in a more severe water depletion than 48 h of dehydration in the normal rats, but also in this group MAP and HR were maintained at values not significantly different from control. Cardiac output (CO) fell during the course of dehydration in both LE and Brattleboro rats. Injection of 20 micrograms/kg of the vasopressin pressor antagonist, 1-deamino-penicillamine, 2-(O-methyl)-tyrosine AVP [dPTyr(Me)AVP] did not decrease MAP or increase HR in LE rats after 24 h of water deprivation and was ineffective even after 48 h of fluid deprivation. CO also remained unchanged following AVP blockade. Efficacy of the antagonist was verified by complete inhibition of the pressor response elicited by exogenous AVP. The concentration of plasma catecholamines was unaltered by dPTyr(Me)AVP. Blockade of the renin-angiotensin system via converting-enzyme inhibition failed to reveal any depressor effect after injection of dPTyr(Me)AVP. Thus it appears that AVP is not involved in the maintenance of blood pressure after fluid deprivation in conscious rats.
Heart rate and plasma catecholamines were determined in 16 patients with alcoholic fatty liver and 14 patients with alcoholic cirrhosis of the liver. The measurements were performed at rest and after exercise on the bicycle ergometer, on average 11 days after admission to hospital. In comparison with a control group, the mean heart rate of the patient group was significantly increased at rest and under graduated loading. Significantly increased plasma catecholamine concentrations under resting conditions were observed in both groups of patients, the increase being more pronounced in the cirrhotics (increased with progressive liver damage, significant differences being found between the control group and each of the two groups of patients). During exercise under a load of 50 or 100 watts, the increases in adrenaline, noradrenaline and dopamine concentrations were greatest in patients with alcoholic cirrhosis. With reference to the initial values, however, the increases in concentration were identical in all three groups. In the patients, metabolism of the catecholamines remained unchanged after an average of 11 days abstinence from alcohol; they showed a significantly diminished elimination of vanillylmandelic acid in the urine and, compared with the greatly elevated plasma catecholamine levels, they showed only a moderate increase in the excretion of catecholamines. The results reported here support the assumption that changes in catecholamine metabolism compatible with an increased sympathetic activity are present in chronic alcoholics without advanced liver damage.
We measured plasma catecholamines, alpha- and beta-adrenoreceptor numbers and the accumulation of cyclic adenosine monophosphate (cAMP) in the unstimulated state and in response to 10 mumol/l (-) isoproterenol in blood cells from 29 euthyroid controls and from 18 patients with spontaneous hyperthyroidism. In the thyrotoxic patients plasma norepinephrine (1.14 +/- 0.5 nmol/l) and epinephrine (0.3 +/- 0.14 nmol/l) were significantly decreased compared with plasma norepinephrine (1.87 +/- 0.7 nmol) and epinephrine (0.41 +/- 0.19 nmol/l) in the controls (P less than 0.01 and P less than 0.05, respectively) and the values obtained in subjects rendered euthyroid by antithyroid treatment (P less than 0.001, respectively). alpha-adrenoceptor density in platelet membranes obtained from patients in the hyperthyroid state (114 +/- 38 sites per cell) was significantly decreased when compared with controls (159 +/- 48 sites per cell, P less than 0.01) and the values from patients under effective antithyroid treatment (136 +/- 35 sites per cell, P less than 0.01). On the contrary, a significant increase in beta-adrenoceptor density in mononuclear leucocyte (MNL) membranes was found in hyperthyroid patients (1751 +/- 237 sites/cell) when compared with controls (1510 +/- 351 sites/cell, P less than 0.05) and the same patients following antithyroid treatment (1455 +/- 260 sites/cell, P less than 0.001). The equilibrium dissociation constants (KD) did not change in hyperthyroidism. Basal cAMP concentrations in MNL were higher in untreated thyrotoxicosis (45 +/- 18 pmol/10(6) cells/10 min) than in patients in the euthyroid state (35 +/- 9 pmol/10(6) cells/10 min, P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
Plasma concentrations of epinephrine, norepinephrine, dopamine and cortisol were determined in four healthy volunteers--resting completely in bed--before and after food intake. Meals were provided at 17.00 h on the first day and at 12.00 h on the second day of the test. Blood samples were drawn every 15 minutes. Epinephrine, norepinephrine, dopamine, and cortisol showed a clear dependence on food intake. After the meals plasma concentrations of the four analytes showed rises, which were more pronounced after lunch at 12.00 h than after dinner at 17.00 h. An increase of epinephrine was observed shortly before meal-times; this could be caused by physiological adaptation to the usual rhythm of food intake and reflex response to expectation of the meal.
In six patients urinary excretion of vanillylmandelic acid and catecholamines (CA) could establish the diagnosis of pheochromocytoma. Free norepinephrine (NE) in plasma was within the normal range in two patients and plasma free epinephrine (E) was only marginally elevated in one of them. The degree of CA conjugation was not altered and scattered as in controls and was therefore not complementary to the usual determination of plasma free CA. The intermittent nature of CA secretion by the tumour could be demonstrated by multiple blood samplings during a 48-h study period in two patients, e.g. normal plasma values might be associated with pheochromocytoma if measurements are made during a trough. Thus a single peripheral CA determination cannot be of discriminative value in the diagnosis of pheochromocytoma unless it shows marked elevation. Ten patients subjected to intracardial measurements and five patients suspected of having a pheochromocytoma underwent venous catheterisation to determine their free and conjugated plasma CA. In controls CA values near the orifices of adrenal veins differed enormously and partly overlapped with corresponding levels of patients with pheochromocytoma. In one patient with surgically proven left adrenal tumour highest concentrations of CA were measured in the vena cava superior. These high CA concentrations, caused by paroxysmal release of CA by the tumour arouse suspicion of an additional, ectopic tumour. Because venous catheterisation cannot be relied on implicitly we propose computed tomographic scanning as a first step in localisation of a pheochromocytoma.
To assess the interaction between adrenergic activity and blood pressure regulation, plasma catecholamines (CA), plasma renin activity (PRA) and plasma aldosteron (PA) were measured in 66 normal subjects and 18 dialysis patients. Prior to dialysis, blood levels of free norepinephrine (NE), epinephrine (E) and PRA were normal, but total (free and conjugated) CA as well as PA were significantly elevated. There was a spectrum of response during hemodialysis. On an average mean arterial blood pressure (MAP) fell during the first two hours of treatment, concomitantly followed by an increase in mean NE level. Whereas PRA and PA were highest at the end of treatment, mean free NE returned promptly to predialysis values through the late dialysis period. Severe hypotensive episodes during dialysis were associated with a baroreceptor-mediated adrenergic stimulation. These results indicate a qualitatively normal reaction of dialysis patients to volume removal and the importance of the renin-angiotensin-system in maintaining blood pressure during dialysis.